© 1995 American Heart Association, Inc.
Articles |
Adenovirus-Mediated Gene Transfer to Normal and Atherosclerotic Arteries
A Novel Approach
From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center and Center on Aging, University of Iowa College of Medicine and Veterans Administration Medical Center, Iowa City, Iowa.
Correspondence to Donald D. Heistad, MD, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242.
Abstract Previous studies of gene transfer to blood vessels
in vivo have relied on intraluminal, catheter-based methods for
delivery of adenoviral and other vectors. In this study, topical
application of a replication-deficient adenoviral vector was used
as an alternative method of gene transfer to the vessel wall. We
administered recombinant adenovirus (1.0 to 1.5x1010
pfu/mL) containing the nuclear targeted bacterial ß-galactosidase
gene topically to arteries in normal and atherosclerotic cynomolgus
monkeys. Topical administration was achieved by injection of adenoviral
suspension within the periarterial sheath. Segments of
femoral and carotid arteries were examined histochemically after
staining with
5-bromo-4-chloro-3-indolyl-ß-D-galactopyranoside 1 day
after treatment with the adenovirus. After topical administration of
virus, ß-galactosidase activity was observed in 
20% of cells
in the adventitia in both normal and atherosclerotic arteries. There
was no detectable ß-galactosidase activity in cells of the intima
or media. Thus, topical application provides an alternative method for
gene transfer to blood vessels in vivo. This approach, which does not
require interruption of blood flow and does not disrupt the
endothelium, may be useful for studies of vascular
biology and perhaps gene therapy in both normal and atherosclerotic
vessels.
Key Words: atherosclerosis • adenovirus • gene therapy • ß-galactosidase
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